People with grandparents from a remote Scottish island are more likely than the rest of the UK population to have a version of a gene that increases cancer risk. One in 40 people with heritage from the island of Whalsay in Shetland have the same variation in the BRCA2 gene – one of the commonest genes linked to breast and ovarian cancer in women, and breast and prostate cancer in men. This genetic change can be passed down from parent to child, affecting multiple members of the same family. The findings suggest that the variant first arrived in an individual who helped found the population on Whalsay more than 300 years ago.Gene changesUniversity of Edinburgh scientists explored how common the variant is by studying genetic information from more than 2000 volunteers with three or more Shetlandic grandparents, in their Viking Genes study.They worked with a team of geneticists from the NHS North of Scotland Genetics Service, who repeatedly found the same single change present in the BRCA2 gene among families from Shetland with breast, ovarian and/or prostate cancer.They discovered the BRCA2 variant in nine volunteers, or 0.4 per cent of those tested, equivalent to one in 230 people. This is 130 times higher than the general UK population, in which 1 in 30,000 people have the same BRCA2 variant.High prevalenceThe findings follow earlier research from the Viking Genes study that found a cancer-causing variant in the related BRCA1 gene, common among people from Orkney.Genetic testing for the two variants would identify more than 90 per cent of people with BRCA changes in the Northern Isles of Scotland. Cancer screening costs for the region would therefore be much lower than the general UK population, which must search for hundreds of variants, the research team says.Early detection of BRCA variants can offer the opportunity to reduce future risk of cancer through lifestyle advice, regular breast screening and risk-reducing surgery, experts say. It is very important to understand that just two gene changes account for more than 90 per cent of the inherited cancer risk from BRCA variants in Orkney and Shetland. This is in stark contrast to the situation in the general UK population, where 369 variants would need to be tested to account for the same proportion of cancer risk from BRCA genes. Any future screening programme for the Northern Isles should therefore be very cost-effective. Professor Jim Flett Wilson Study lead, from the University of Edinburgh’s Usher Institute Developing cancer is not solely down to carrying the BRCA2 variant, there are many complex factors, and some people with the gene variant will not get cancer. However, we know that testing and the right follow-up can save lives. Many people who carry a gene variant are unaware of it. Biological relatives of people with the BRCA2 variant are encouraged to consider being tested Professor Zosia Miedzybrodzka Professor of Medical Genetics at the University of Aberdeen and Director of the NHS North of Scotland Genetic Service Genetic testing is available to relatives of people with the known BRCA2 variant as standard NHS care. Testing can also be requested by people with at least one Whalsay grandparent and who have themselves, or a close relative, been affected by breast, ovarian or prostate cancer. More information is available from the NHS North of Scotland Genetic Service.The study, funded by the Medical Research Council and Wellcome, was supported by Edinburgh Innovations and the Wellcome iTPA programme. Genetic sequencing of anonymised DNA samples was conducted by Regeneron Genetics Center.Related linksRead the research publication in the European Journal of Human GeneticsGuidance from NHS North of Scotland Genetic ServiceViking Genes studyImage credit: Holger Leue via Getty Images Tags 2024 Publication date 24 Oct, 2024
